Freeze-drying has gained ground especially in the pharmaceutical industry for the preservation of medications, vaccines etc. In the chambers of modern freeze-drying devices, a plurality of storage plates are located, the storage plates having storage surfaces that can accommodate a multitude of containers, bottles or the like (100,000 or more). The product, which is generally dissolved in water, is filled into containers of this type. Before starting the freeze-drying process, the liquid is frozen. This step generally already occurs in the chamber of the freeze-drying unit by cooling the storage surfaces to an accordingly low temperature (−40° C. to −60° C.).
German disclosure document 197 19 298 (U.S. Pat. No. 6,163,979 to Oetjen et al.) discloses a chamber of the aforementioned kind. Moreover, the German document explains a method for controlling the freeze-drying process in the chamber. The characteristics of the course of the drying process are essentially two drying phases. As long as there is still crystalline (frozen) water within the product, the drying phase is referred to as the main or sublimation drying process. When water is no longer present in the form of ice, the remaining water has been absorbed by the dry product or more or less firmly bonded thereto as well. Removal of this remaining water takes place during the subsequent, after drying or desorption drying process. To control a freeze-drying process of this type, certain chamber pressures and storage surface temperatures must be obtained. An essential parameter is the ice temperature, which can be determined by measurements of pressure increase.
Controlling the ice temperature in the sublimation surface via the pressure assumes that a uniform water vapor partial pressure exists in the chamber. This uniform pressure distribution is possible only to a limited extent in the area of the chamber walls as well as the chamber door or doors. In these areas, the temperature of the product that is located in the bottles depends not only on the storage plate temperature, but is also affected by the temperature of the interior walls of the chamber through thermal radiation. If, for example, the water vapor being released from the product has a temperature of −40° C., then the temperature on the storage plates increases, for example, to −20° C., while the water vapor in the vicinity of the walls, for example, reaches 20° C. Due to these differences in temperature, pressure differences of more than 10% can develop. The desired prerequisite that a uniform water vapor partial pressure be maintained in the chamber is no longer met with sufficient accuracy; the ice temperature that develops is no longer uniform. Product quality losses are the resulting consequence.
In order to avoid the influence of the chamber wall temperature on the temperature of the product contained in the bottles, it is known to equip the storage plates with an outer rim, which protects the product from heat radiation originating from the chamber walls. These measures, however, have had only limited success because the differences in temperature between the rim and the storage surfaces are about 20° C.
Moreover the suggestion has been made to regulate the temperatures of the walls and door(s) of the chamber. These measures, however, are associated with practically unsolvable technical difficulties and economic disadvantages. The chamber with its door(s) in production facilities can, especially if vapor sterilization is required, reach a mass of many tons. Said masses would have to be cooled down to −40° C. and often even down to −60° C. during the freezing process, which leads either to an impermissibly long freezing time or to separate cooling systems, which have to achieve a multiple of the cooling output that is required for the storage plates and the product. Apart from these economic problems, it is technically difficult to cool the flanges on the chamber and the flange on the door to e.g. −50° C. The seals between the chamber and the door must remain functional at low temperatures, and it is difficult to avoid water vapor condensation on said flanges. Insulating the flange against water vapor condensation is technically not possible because the chamber flange and the door are located in sterile rooms. The sterility requirements in a clean room exclude the use of insulating materials that would be suitable for these low temperatures.
The present invention proposes a chamber for a freeze-drying device of the aforementioned kind that maintains uniform temperature conditions and water vapor pressure conditions during the freeze-drying process without special technical modifications.